%0 Journal Article
%T TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.
%A Xu C
%A Cao J
%A Qiang H
%A Liu Y
%A Wu J
%A Luo Q
%A Wan M
%A Wang Y
%A Wang P
%A Cheng Q
%A Zhou G
%A Sima J
%A Guo Y
%A Xu S
%J Genome Biol
%V 25
%N 1
%D 2024 Jul 7
%M 38972974
暂无%R 10.1186/s13059-024-03326-3
%X Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.